Camptothecin (Chem. Abstracts Registry No. 7689-03-4) is a naturally occurring compound found in Camptotheca acuminata (Nyssaceae) which has antileukemic and antitumor properties. Numerous camptothecin analogs having like properties are known, examples being those described in U.S. Pat. No. 4,894,456 to Wall et al. and European Patent Application No. 0 325 247 of Yaegashi et al.
A number of syntheses for camptothecin are known. Several routes are reviewed in Natural Products Chemistry, Vol. 2, 358-361 (K. Nakanishi, T. Goto, S. Ito, S. Natori and S. Nozoe eds.) and in J. Cai and C. Hutchinson, Camptothecin, in The Alkaloids, Vol. XXI, 101-137 (Academic Press 1983). The biosynthesis of camptothecin is described in Natural products Chemistry, Vol. 3, 573-574 (K. Nakanishi et al. eds.). One synthetic route is described in U.S. Pat. No. 4,894,456 to Wall et at.
U.S. Pat. No. 5,162,532 to Comins and Baevsky describes a parallel synthesis for camptothecin and camptothecin analogs, where compounds of Formula I are prepared by scheme A: ##STR1##
In U.S. Pat. No. 5,212,317 to Comins and Baevsky, compounds of Formula III in scheme A above are prepared in asymmetric form in accordance with scheme C below: ##STR2##
An object of the present invention is to provide new methods for preparing compounds of Formula III above and useful for making such compounds, all of which are useful for the synthesis of camptothecin and camptothecin analogs.